With substantial completion of the first human genome sequencing project, considerable attention has turned to a determination of the biologic function of various DNA sequences. This investigation, often termed “functional genomics” represents a new phase of genome analysis. Specifically, functional genomics refers to the development and application of global (genome-wide or system-wide) experimental approaches to assess gene function by making use of the information and reagents provided by structural genomics. It is typically characterized by high throughput or large-scale experimental methodologies combined with statistical and computational analysis of the results.
One fundamental strategy in a functional genomics approach is to expand the scope of biological investigation from studying single genes or proteins to studying all genes or proteins at once in a systematic fashion. Computational biology will perform a critical and expanding role in this area: whereas structural genomics has been characterized by data management, functional genomics will be characterized by mining the data sets for particularly valuable information. Functional genomics promises to rapidly narrow the gap between sequence and function and to yield new insights into the behavior of biological systems.
One important class of genes includes those genes that encode cell surface molecules and receptors. Receptors typically bind ligands resulting in the delivery of a signal into the cell (signaling). This can lead to a number of biologic functions including, but not limited to cell growth, cell replication, cell death, etc. Other receptors mediate the specific transfer of molecules from outside the cell into the cytoplasm (endocytosis or internalization). Endocytosis is also an important mechanism by which receptor signaling is modulated. Different cell types have qualitatively and quantitatively different surface receptors and the pattern of receptor expression may change dramatically with the development and/or differentiation of a cell or tissue and/or the development and progression of a disease.
Identification of such receptors and the development of specific receptor ligands, allows the study of receptor function and the determination of the temporal-spatial pattern of receptor expression. For example, such ligands can be used to profile the pattern of receptor expression across different cell types upon exposure to a drug or during the development of a disease. In addition, cell-specific receptor ligand, more preferably internalizing cell specific receptor ligands can be used to target drugs or markers to the cell surface or into the cytoplasm (for internalizing receptors), e.g. for therapeutic effect.